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Structure-based design and synthesis of macrocyclic human rhinovirus 3C protease inhibitors |
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| Authors: | Kenji Namoto Finton Sirockin Holger Sellner Christian Wiesmann Frederic Villard Robert J. Moreau Eric Valeur Stephanie C. Paulding Simone Schleeger Kathrin Schipp Joachim Loup Lori Andrews Ryann Swale Michael Robinson Christopher J. Farady |
| Affiliation: | 1. Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland;2. Novartis Institutes for BioMedical Research, 5300 Chiron Way, Emeryville, CA 94608-2916, USA |
| Abstract: | The design and synthesis of macrocyclic inhibitors of human rhinovirus 3C protease is described. A macrocyclic linkage of the P1 and P3 residues, and the subsequent structure-based optimization of the macrocycle conformation and size led to the identification of a potent biochemical inhibitor 10 with sub-micromolar antiviral activity. |
| Keywords: | Rhinovirus 3C protease Protease inhibition Covalent inhibitor Macrocycle Structure-based drug design Solid phase synthesis |
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